Cocaine is considered to be the most addictive of all substances of abuse. Estimates for 2006 suggest that over half of all illicit drug-based emergency department visits involved cocaine, with 548,608 occurrences, and account for 181 visits per 100,000 people in the US.
Chronic cocaine intake causes brain cells to adapt functionally to strong imbalances of transmitter levels in order to compensate extremes. Thus, receptors disappear from the cell surface or reappear on it, resulting more or less in an “off” or “working mode” respectively, or they change their susceptibility for binding partners (ligands). However, studies suggest cocaine abusers do not show normal age-related loss of striatal DAT sites, indicating that cocaine has neuroprotective properties for dopamine neurons. The experience of insatiable hunger, aches, insomnia/oversleeping, lethargy, and persistent runny nose are often described as very unpleasant. Depression with suicidal ideation may develop in very heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes indicates a long term damage of dopamine neurons. All these effects contribute to a rise in tolerance thus requiring a larger dosage to achieve the same effect.
Physical side effects from chronic use of cocaine include hemoptysis, bronchospasm, pruritus, fever, diffuse alveolar infiltrates without effusions, pulmonary and systemic eosinophilia, chest pain, lung trauma, sore throat, asthma, hoarse voice, dyspnea (shortness of breath), and an aching, flu-like syndrome.
Chronic intranasal usage can degrade the cartilage separating the nostrils (the septum nasi), leading eventually to its complete disappearance. Due to the absorption of the cocaine from cocaine hydrochloride, the remaining hydrochloride forms a dilute hydrochloric acid.
Cocaine may also greatly increase the risk of developing rare autoimmune or connective tissue diseases such as lupus, Goodpasture's disease, vasculitis, glomerulonephritis, Stevens-Johnson syndrome and other diseases. It can also cause a wide array of kidney diseases and renal failure. Cocaine abuse doubles both the risks of hemorrhagic and ischemic strokes, as well as increases the risk of other infarctions, such as myocardial infarction.
The devastating medical and social cost of cocaine addiction and overdose make discovery of pharmacological agents to block the addictive effects of cocaine an important goal.